Abstract

Aspirin and clopidogrel are cornerstone therapies in cardiovascular disease. In particular, they are almost universally prescribed in patients undergoing percutaneous coronary intervention (PCI). Evidence has emerged of a variation in the antiplatelet effects of aspirin and clopidogrel between individual patients with a suggestion of an increased risk of adverse cardiovascular events. However, the optimal method of measuring response to aspirin and clopidogrel remains uncertain. In light of this, the antiplatelet effects of both aspirin and clopidogrel were studied in patients with coronary artery disease, concentrating on patients undergoing PCI.

Initially, a pilot study of 40 patients investigated the use of thromboxane B2 (TxB2), VerifyNow Aspirin, VerifyNow P2Y12, platelet fibrinogen binding and intra-platelet vasodilator-stimulated phosphoprotein levels (VASP-PRI) to measure response to aspirin and clopidogrel. This was followed by a larger study assessing aspirin and clopidogrel response in 323 patients attending for coronary angiography with a view to PCI. These patients were tested by measuring TxB2, VerifyNow P2Y12, VASP and whole blood impedance platelet aggregation (WBPA). The primary objective was to investigate whether measures of aspirin or clopidogrel efficacy predicted peri-procedural myocardial necrosis following PCI. In addition, a small series of 10 patients had aspirin and clopidogrel response measured following stent thrombosis.

A wide variation in the antiplatelet effects of both aspirin and clopidogrel was found by all measures. Correlation between assays ranged from moderate to poor. Of particular interest, it was found that measurement of [TxB2] may facilitate the assessment of aspirin response in patients already taking clopidogrel. There was a high incidence of myocardial necrosis following coronary intervention assessed by elevation of troponin I. Only VerifyNow P2Y12 and VASP-PRI were associated with a significantly increased frequency of myocardial necrosis following PCI.

The data of this thesis confirm a wide variation in response to aspirin and clopidogrel. Good response to clopidogrel was associated with reduced myocardial necrosis during PCI. TxB2 may be the best measure of aspirin response for patients taking both therapies. How these measures may be incorporated into clinical practice remains uncertain.